Naying He¹, Kiarash Ghassaban^2,3, Pei Huang⁴, Zenghui Cheng¹, Yan Li¹, Mojtaba Jokar⁵, Sean K. Sethi^2,5, Weibo Chen⁶, Shengdi Chen⁴, Fuhua Yan¹, and Ewart Mark Haacke^1,2,5
1Radiology, Ruijin Hospital, Shanghai Jiaotong Univ. School of Medicine, Shanghai, China, Shanghai, China, ²Department of Radiology, Wayne State University, Detroit, MI, United States, ³Department of Biomedical Engineering, Wayne State University, Detroit, MI, United States, ⁴Department of Neurology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China, ⁵Magnetic Resonance Innovations, Inc., Bingham Farms, Bingham Farms, MI, United States, ⁶Philips Healthcare, Shanghai, China

A total of 40 Parkinson’s disease (PD) patients and 40 age- and sex-matched healthy controls (HC) were scanned using a single 3D gradient echo magnetization transfer sequence to measure neuromelanin and iron content, and the overlap between them. These measures showed reliable results indicative of powerful diagnostic biomarkers to differentiate PD patients from HCs. An increase in iron content was seen in the substantia nigra for the PD patients while the neuromelanin volume decreased. The best predictor, however, was found to be the combination of neuromelanin volume and its overlap with iron-containing substantia nigra which yielded an AUC of 98%.

Jason Langley¹, Daniel E Huddleston², Evan Oculam³, Stewart Factor², and Xiaoping Hu^1,3
1Center for Advanced Neuroimaging, University of California Riverside, Riverside, CA, United States, ²Neurology, Emory University, Atlanta, GA, United States, ³Bioengineering, University of California Riverside, Riverside, CA, United States

Parkinson’s disease is a progressive, neurodegenerative disorder characterized by asymmetrical onset of motor symptoms such as bradykinesia, rigidity, and tremor. The principal pathology in Parkinson's disease is the loss of melanized dopamine neurons in the substantia nigra pars compacta (SNpc) with iron deposited alongside this neuronal loss.  Loss of SNpc neurons should remove barriers for diffusion and increase diffusivity of water molecules in regions undergoing this loss.  Studies examining Parkinsonian SNpc microstructural changes using a single tensor model have yielded conflicting results. Here, we investigate PD-related microstructural changes in multiple compartment and single tensor models.

Emma Biondetti^1,2,3, Rahul Gaurav^1,2,3, Lydia Yahia-Cherif^1,3, Graziella Mangone⁴, Nadya Pyatigorskaya^1,2,3,5, Romain Valabrègue^1,3, Claire Ewenczyk^2,3, Matthew Hutchison⁶, Jean-Christophe Corvol^3,4,7, Marie Vidailhet^2,3,7, and Stéphane Lehéricy^1,2,3,5
1Brain and Spine Institute - ICM, Centre for NeuroImaging Research - CENIR, Paris, France, ²Brain and Spine Institute - ICM, Team "Movement Investigations and Therapeutics", Paris, France, ³Brain and Spine Institute - ICM, INSERM U 1127, CNRS UMR 7225, Sorbonne University, Paris, France, ⁴National Institute of Health and Medical Research - INSERM, Clinical Investigation Centre, Pitié-Salpêtrière Hospital, Paris, France, ⁵Department of Neuroradiology, Pitié-Salpêtrière Hospital, Public Assistance - Paris Hospitals (AP-HP), Paris, France, ⁶Biogen Inc., Cambridge, MA, United States, ⁷Department of Neurology, Pitié-Salpêtrière Hospital, Public Assistance - Paris Hospitals (AP-HP), Paris, France

Parkinson's disease (PD) and idiopathic rapid eye movement sleep behaviour disorder (iRBD, a prodromal condition of Parkinsonism) are characterised by the progressive loss of neuromelanin-containing neurons in the substantia nigra (SN). Based on longitudinal neuromelanin-sensitive magnetic resonance imaging (NM-MRI) of healthy controls, patients with iRBD and patients with PD, and voxel-wise analysis of NM-MRI on a study-specific anatomical brain template, we showed the temporal evolution of SN atrophy in disease. We also found significant correlations between temporal changes in the NM-MRI signal-to-noise ratio and clinical scores of disease severity, reflecting the functional organisation (motor, cognition and behaviour/mood) of the SN.

María Guadalupe García-Gomar¹, Kavita Singh¹, Matthew Stauder², Laura D. Lewis¹, Lawrence L. Wald¹, Bruce R. Rosen¹, Aleksandar Videnovic², and Marta Bianciardi^1
1Department of Radiology, Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital and Harvard Medical School, Boston, MA, United States, ²Department of Neurology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, United States

REM-sleep-behavior-disorder (RBD) is a sleep disorder characterized by the absence of muscular atonia during REM sleep. RBD patients have a high risk of developing Parkinson’s disease (PD) within 10 years from RBD diagnosis. Thus, RBD allows the investigation of early/prodromal neurodegenerative-stages. Changes in brainstem-nuclei-connectivity are expected in RBD/prodromal-PD based on animal and ex-vivo human-studies. Yet, their investigation in living-humans is understudied. Through high-spatial-resolution 7 Tesla HARDI MRI and a recently-developed probabilistic-brainstem-nuclei-atlas, we built a brainstem-based structural-connectome in living RBD-patients and age-matched controls. Interestingly, in RBD-patients we detected structural-connectivity-changes within the brainstem in line with the pathophysiology of RBD in animal-models.

Tao Guo¹, Xiaojun Guan¹, Cheng Zhou¹, Ting Gao², Jingjing Wu¹, Peiyu Huang¹, Xiaojun Xu¹, and Minming Zhang^1
1Department of Radiology, Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, China, ²Department of Neurology, Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, China

We establish brain connectivity features that represented the disease signatures and identify Parkinson’s disease (PD) subtypes by data-driven approaches. Canonical correlation analysis (CCA) was performed to define the clinical related connectivity features, which were then used in hierarchical cluster analysis to identify the distinct biotypes of PD. Multimodal MRI including gray matter functional connectivity and white matter microstructure were further used to explore the neuropsychological significance of these biotypes. CCA revealed two significant clinical-related patterns in PD. Hierarchical cluster analysis identified three neurophysiological biotypes: mild, progressive depression-dominant and progressive motor-dominant. These three biotypes characterized by different neural substrate.

Song'an Shang¹, Weiqiang Dou², Hongying Zhang³, Jing Ye³, and Jingtao Wu^3
1Department of Radiology, Nanjing First Hospital, Nanjing Medical University, Nanjing, China, ²GE Healthcare, MR Research China, Beijing, China, ³Northern Jiangsu People’s Hospital, Yangzhou, China

In this study, we aimed to investigate the association of Apolipoprotein E (ApoE) gene polymorphism and caudate functional connectivity in mild cognitive impairment of Parkinson’s disease (PD-MCI), using resting-state functional magnetic resonance imaging (rs-fMRI) and genotyping. Our findings revealed that gene-brain-behavior associations involve alterations of caudate activity with posterior cortical, thereby provide potential imaging-based markers that contribute to the early diagnosis and monitoring of PD-MCI.

Yao Chia Shih¹, Septian Hartono^2,3, Amanda Choo², Celeste Chen², Isabel Chew¹, Zheyu Xu^2,3, Louis Tan^2,3, ChingYu Cheng^3,4, Eng King Tan^2,3, and Ling Ling Chan^1,3
1Department of Diagnostic Radiology, Singapore General Hospital, Singapore, Singapore, ²Department of Neurology, National Neuroscience Institute – SGH Campus, Singapore, Singapore, ³Duke-NUS Medical School, Singapore, Singapore, ⁴Department of Ophthalmology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore

White matter microstructural changes in relation to the neurotransmitter systems in Parkinson’s disease (PD) progression remains unclear. We used diffusion spectrum imaging and local connectome fingerprint analysis to investigate microstructural integrity of the the premotor and motor pathways in associations with various neurotransmitter systems in the brainstem, and disease duration and severity of motor-related symptoms. We found greater microstructural changes in the dopaminergic pathways in association with motor progression than for the other neurochemical pathways. Patients with longer disease duration or more severe motor dysfunctions showed increased anisotropic water diffusion in these pathways, suggesting a compensatory effect of axonal sprouting.

Shumyla Jabeen¹, Jitender Saini¹, Jaladhar Neelavalli², Narayankrishna Rolla², Shweta Prasad³, and Ravi Yadav^4
1Neuroimaging and Interventional Radiology, National Institute of Mental Health and Neurosciences, Bangalore, India, ²Philips India, Bangalore, India, ³Clinical neurosciences, National Institute of Mental Health and Neurosciences, Bangalore, India, ⁴Neurology, National Institute of Mental Health and Neurosciences, bangalore, India

Tremor dominant PD and ET often pose a diagnostic difficulty in view of overlapping clinical features. We aimed at distinguishing the two using the novel technique of QSM to measure iron deposition in various gray matter nuclei including the substantia nigra pars compacta(SNPc). A statistically significant difference was seen in the QSM values of the SNPc, SNPr  and caudate nucleus. ROC curve analysis showed a sensitivity and specificity of 90 and 87.5% respectively using a cut off value of 12 ppb for the SNPc. Thus, QSM is a potentially useful problem solving technique for distinguishing tremor dominant PD from ET.

Na Wang¹, XueLing Liu², and YuXin Li^2
1Fudan university Huashan hospital, Shanghai, China, ²Huashan Hospital, Fudan University,, Shanghai, China

Whether swallow tail sign (STS) could serve as a substitute or complement for nuclear medical imaging remains unclear. In this study, we compared STS features on MRI with striatal uptake on positron emission tomography (PET) at per nuclei level, construct an evaluation scale based on bilateral STS changes at the patient level, and estimate the diagnostic performance of the scale in 39 early-stage PD and 28 healthy controls. STS alterations corresponded well with striatal uptake on PET in early-stage PD. Total loss of STS is a reliable sign of nigrostriatal dopaminergic degeneration and might be a potential substitute for PET.

Yuhui Xiong^1,2, Lanxin Ji¹, Le He¹, Li Chen³, Xue Zhang¹, Zhensen Chen³, Xuesong Li⁴, Huilin Zhao³, Manabu Shirakawa³, Chun Yuan³, Yu Ma⁵, and Hua Guo^1
1Center for Biomedical Imaging Research, Department of Biomedical Engineering, School of Medicine, Tsinghua University, Beijing, China, ²Neusoft Medical Systems Co., Ltd., Shanghai, China, ³Vascular Imaging Laboratory, Department of Radiology, University of Washington, Seattle, WA, United States, ⁴School of Computer Science and Technology, Beijing Institute of Technology, Beijing, China, ⁵Tsinghua University Yuquan Hospital, Beijing, China

Parkinson’s Disease (PD) has shown to be associated with cerebrovascular abnormalities, but its non-dopaminergic pathological mechanism is less studied. This study investigated the regulatory effect of levodopa, the most-commonly used therapy for PD, on cerebral arteries and blood flow. 57 PD patients and 17 age-matched healthy controls were scanned for artery morphologic and cerebral perfusion imaging at baseline, then the patients were re-scanned 50 minutes after taking levodopa. Results indicated that levodopa elevated blood perfusion level of PD brains to normal levels and dilated proximal arteries. Plus, blood perfusion showed related to motor syndrome scale post-levodopa.